Lung damage following hyperoxic exposure is in large part due to increased rates of tissue oxygen radical formation. These oxygen radicals can react with membrane constituents, inhibit enzyme systems, deplete cells of critical metabolic intermediates and ultimately cause cell death. Superoxide dismutase and catalase have been shown by many investigators to be critical in maintining low intracellular levels of 02- and H202, respectively. In addition, these enzymes have been shown to protect lung endothelial cells from damage due to 02- and H202 released by activated leukocytes. This proposed investigation will determine the ability of superoxide dismutase catalase and/or vitamin E-contaning phospholipid vesicles to augment pulmonary capillary endothelial cell defenses, modulate cellular oxygen radical production and prevent the lethality of animal exposure to 100 percent oxygen. Superoxide dismutase, catlase and vitamin E will be encapsulated in unilamellar phospholipid vesicles consisting of phospholipid, 14C-phospholipid, cholesterol and stearylamine. In cases, trace amounts of 125I-labelled superoxide dismutase and catalase will be added to unlabeled enzymes encapsulated in phospholipid vesicles so that cellular and organ distribution of both vesicle lipid and contents can be determined. the antioxidant enzyme content of both cultured endothelial cells and rat lungs in vivo will be augmented by incubation with or injection of vesicle preparations. Subcellular distribution of added enzymes will be determined. The CN- resistant respiration, hydrogen peroxide production and hydroxyl radical formation (all measures of cellular oxygen radical production) of cultured lung endothelial cells and whole lung preparations will be measured under normoxic and hyperoxic conditions, before and after augmention with superoxide dismutase, catalase and superoxide dismutase plus catalase. The kinetics of appearance and persistence of vesicle encapsulated enzymes will be measured in the circulation and ungs of rats. Then, the effect of antioxidant enzyme supplementation will be studied by measuring effects on the times of 50 percent and 100 percent mortality of rats breathing 100 percent oxygen.